Annals of medicine
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Review
CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response.
CD163 is a hemoglobin scavenger receptor exclusively expressed in the monocyte-macrophage system. A particularly high expression is seen in macrophages of the 'alternative activation' phenotype playing a major role in dampening the inflammatory response and in scavenging components of damaged cells. CD163-mediated endocytosis of haptoglobin-hemoglobin complexes formed upon red blood cell hemolysis leads to lysosomal degradation of the ligand protein and metabolism of heme by cytosolic heme oxygenase. ⋯ In addition to being present on the macrophage surface, continuous shedding of the extracellular domain of CD163 leads to substantial amounts of soluble receptor in plasma. An increased shedding is due to inflammatory stimuli, and a role for soluble CD163 in immune suppression has been proposed. Furthermore, recent data indicate that soluble CD163 may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions.
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Hypertrophic cardiomyopathy (HCM) is a genetically and clinically heterogeneous myocardial disease caused by mutations in genes encoding sarcomeric proteins. To assess the genetic background and phenotypic expression of HCM in eastern Finland, we screened 35 unrelated patients with HCM from the Kuopio University Hospital area for variants in 9 genes encoding sarcomeric proteins with the PCR-SSCP method. We herewith describe our previous findings in five sarcomeric genes and also report hitherto unpublished data on four additional sarcomeric genes. ⋯ Altogether, the aforementioned 6 mutations found in MYBPC3, TPM1, and MYH7 accounted for 61% of familial and 40% of all HCM cases. The mutations were associated mostly with benign or intermediary phenotypes with only few HCM-related deaths. We conclude that the genetic profile of HCM in eastern Finland is unique, characterized by few founder mutations with benign or intermediary phenotypes.
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Patients with the 3243A > G mutation in mitochondrial DNA (mtDNA) have an increased risk for cardiovascular morbidity and mortality. The function of the autonomic nervous system has not been evaluated in these patients. ⋯ Patients with the 3243A > G mutation in mtDNA have abnormalities in the spectral and fractal characteristics of HRV suggesting altered cardiac autonomic regulation. The abnormalities are not clearly associated with clinical manifestations related to 3243A > G suggesting that mitochondrial dysfunction may affect the autonomic regulatory systems more directly.
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Leptin is best known as a regulator of energy homeostasis, but it also interacts with sleep and breathing. Leptin secretion increases at night and decreases during the day. The circadian secretory profile of leptin is determined both by the hypothalamic circadian pacemaker and sleep-wake cycle. ⋯ Serum leptin levels are higher in obstructive sleep apnoea syndrome but lower during extended sleep deprivation in healthy subjects or in narcolepsy. Abnormalities in serum leptin concentrations have recently been linked with deleterious effects on weight control, cardiovascular health and glucose regulation. Since sleep curtailment and sleep-disordered breathing are epidemics of the modern society, better understanding of leptin pathophysiology could open new perspectives to pathophysiology of major public diseases, including obesity and metabolic syndrome.
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Prolactin (PRL) is one of a family of related hormones including growth hormone (GH) and placental lactogen (PL) that are hypothesized to have arisen from a common ancestral gene about 500 million years ago. Over 300 different functions of PRL have been reported, highlighting the importance of this pituitary hormone. PRL is also synthesized by a number of extra-pituitary tissues including the mammary gland and the uterus. ⋯ This activates a number of signaling pathways resulting in the transcription of genes necessary for the tissue specific changes induced by PRL. Mouse knockout models of the major forms of the PRL receptor have confirmed the importance of PRLs role in reproduction. Further knockout models have provided insight into the importance of PRL signaling intermediates and the advent of transcript profiling has allowed the elucidation of a number of PRL target genes.